Doxycycline PEP for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV PrEP (dPEP-KE)

PrEP and dPEP: Doxycycline Post-exposure Prophylaxis for Prevention of Sexually Transmitted Infections Among Kenyan Women Using HIV Pre-exposure Prophylaxis

This is a randomized clinical trial of doxycycline post-exposure prophylaxis (dPEP) to reduce bacterial STIs among Kenyan women taking pre-exposure prophylaxis (PrEP). The overarching goal is to assess the effectiveness of dPEP on incidence of STIs while also balancing acceptability, cost, and impact on tetracycline resistance to inform public health policy. Participants will be randomized to receive dPEP and standard of care or the standard of care only. Questionnaires, focus group discussions, SMS, and in-depth interviews will be used to study acceptability and changes sexual behavior due to dPEP.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Infections; HIV/AIDS; Neisseria Gonorrheae Infection; Chlamydia Trachomatis Infection; Syphilis Infection
• Intervention / Treatment: Drug: Doxycycline

Detailed Description

This study is an open-label 1:1 randomized clinical trial of doxycyline PEP to reduce bacterial STIs - Neisseria gonorrhoeae, Chlamydia trachomatis, and T. pallidum (syphilis) - among Kenyan women taking PrEP. Participants will be counseled about the preliminary effectiveness data from IPERGAY, and the potential for resistance in STIs or other bacteria.

The primary study objectives are to 1) evaluate the effectiveness of doxycycline PEP (dPEP) to reduce STI infections in HIV-uninfected Kenyan women taking HIV PrEP; 2) assess the safety, tolerability, and acceptability of dPEP; 3)assess adherence to dPEP; 4) investigate the impact of dPEP on tetracycline resistance in N. gonorrhoeae and C. trachomatis; 5) measure the cost of dPEP and estimate the cost per case averted, budget impact, and affordability

Subjects will be randomized 1:1 to dPEP versus standard of care; randomization will be done in variable-sized blocks and using opaque envelopes opened at randomization. Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act (consistent with IPERGAY) as frequently as daily if indicated but not more than once daily.

At Months 0,3,6 and 9, women randomized to dPEP will receive doxycycline, sufficient for up to daily use for 3 months (i.e., 180 capsules). Unused capsules will be counted at each quarterly follow-up visit and additional doxycycline will be provided. Participants will also be offered single- or multi-dose pill carriers for ease of dosing dPEP following exposures. All participants will receive quarterly visits for standard of care prevention services and collection of clinical and behavioral data, for a total of 12 months of follow-up.

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kenya
  • Kisumu, Kenya
    • Kenya Medical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willing and able to give written informed consent
• Age ≥18 years and ≤30 years old
• Female sex at birth
• HIV-seronegative at the time of last test within the past month and a current prescription for PrEP according to the national guidelines of Kenya (define PrEP eligibility as: partner of HIV-infected person not on ART or on ART for <6 months, >1 partner of unknown status, transactional sex, recent STI, recurrent HIV PEP use, inconsistent condom use, or injection drug use).

Exclusion Criteria:

• Pregnant
• Breastfeeding a child
• Allergy to tetracycline class
• Current medications which may impact doxycycline metabolism or that are contraindicated with doxycycline, as per the prescribing information. These include systemic retinoids, barbiturates, carbamazepine, phenytoin, and warfarin.
• Recent use of prolonged (more than 14 day course) antibiotics in the month prior to enrollment
• Active, clinically significant medical or psychiatric conditions that would interfere with study participation, at the discretion of the site investigator or designee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dPEP Intervention Arm; Participants assigned to dPEP will be instructed to take doxycycline 200 mg (two 100mg capsules) orally within 24 hours and up to 72 hours after each condomless sex act	Drug: Doxycycline; 200 mg of doxycycline to be taken orally within 24 hours and up to 72 hours after each condomless sex act
No Intervention: Standard of Care Arm; Participants assigned to Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by laboratory-based diagnosis	Combined incidence of N. gonorrhoeae, C. trachomatis, or early syphilis infection by by laboratory-based diagnosis (e.g., positive N. gonorrhoeae or C. trachomatis based on NAAT or syphilis based on four-fold increase in non-treponemal titers).	12 months post enrolment

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of California, San Francisco; Kenya Medical Research Institute; Kenya National AIDS & STI Control Programme
• Investigators: Principal Investigator: Jared Baeten, MD, PhD, University of Washington

Publications and helpful links

General Publications

• Stewart J, Bukusi E, Sesay FA, Oware K, Donnell D, Soge OO, Celum C, Odoyo J, Kwena ZA, Scoville CW, Violette LR, Morrison S, Simoni J, McClelland RS, Barnabas R, Gandhi M, Baeten JM. Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial. Trials. 2022 Jun 16;23(1):495. doi: 10.1186/s13063-022-06458-8.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): October 30, 2022
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Sexually Transmitted Infections
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Sexually Transmitted Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Gonorrhea; Sexually Transmitted Diseases; Syphilis; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: STUDY00007487; R01AI145971 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes